Trial achieved its primary endpoint of pathological Complete Response Rate
Trial achieved its secondary endpoint in operability (R0 rate)
NBTXR3 demonstrated significant superiority and clinical benefits for patients versus standard of care
Safety profile confirmed
Randomized trial validated the first-in-class mode of action of NBTXR3
NANOBIOTIX (Euronext: NANO – ISIN: FR0011341205), a late clinical-stage nanomedicine company pioneering new approaches in the treatment of cancer, announced today positive topline results of the Phase II/III act.in.sarc trial evaluating NBTXR3 in Soft Tissue Sarcoma (STS).
“Data are exceptional and show without any doubt an improvement of radiation therapy impact with a significant number of complete response. NBTXR3 can bring real benefit to patients and it can change the standard of care. This innovation will play a role in many other indications and particularly where radiotherapy is used alone.”
Pr. Sylvie Bonvalot, MD, Head of Sarcoma and Complex Tumor Surgery Unit at Institut Curie, Paris, France and Global Principal Investigator of the PII/III study
NBTXR3 is a first-in-class product with a new mode of action physically destroying cancer cells when activated by radiation therapy. NBTXR3 is designed to directly destroy tumors and activate the immune system for both local control and systemic disease treatment.
The Phase II/III study was a prospective, randomized (1:1), multinational, open label and active controlled two-armed study of 180 patients with locally advanced STS. The objective of the Phase II/III trial was to evaluate the efficacy and the safety of NBTXR3 activated by radiotherapy compared to the standard of care (radiotherapy alone). Patients have been treated with the standard dose of radiation (25×2 Gy) and efficacy endpoints have been measured on surgically resected tumors.
Primary endpoint achieved in the intend-to-treat population (ITT)
The primary endpoint is the pathological Complete Response Rate (pCRR) defined as the rate of patients showing less than 5% of residual viable cancer cells in the tumor post treatment. This primary endpoint is related to NBTXR3’s mode of action and product efficacy. Twice as many patients (16.1% vs 7.9%) achieved a pathological Complete Response (pCR) with NBTXR3 compared to the control arm (p = 0.0448). The significant difference observed between both arms validates the superiority of the treatment with NBTXR3 versus radiation alone.
Secondary Endpoint achieved in the ITT – Resection margins status and operability
The main secondary endpoint is the resection margin status evaluating the quality of surgery. The main objective is to achieve compartmental clean margins (negative margin defined as R0) i.e. no more cancer cells found within the surgical margins. NBTXR3 demonstrated a statistically significant increase in R0 surgical margin rate compared to radiotherapy alone (relative increase of 20%, p = 0.042). The resection with negative margins is a validated surrogate endpoint for systemic and long-term benefit for patients such as local progression free survival (PFS) and distant PFS.
Pr Jean-Yves Blay, MD, Director of the Centre Léon Bérard, Lyon, France, commented, “I am amazed by the difference of Response Rate, it is extremely uncommon to double the Rate of Complete histological Response and I do not see any other strategy able to accomplish that. Even more impressive is the R0 rate, which is increased by more than 20% compared to an average rate of 64%. This difference is really impressive, considering that R0 impacts patients relapses and survival.”
Safety and feasibility
NBTXR3 demonstrated a good local tolerance among this patient’s population. Findings showed a very similar radiation-related safety in both arms. The patients in both the control and tested arms of the study received the planned radiotherapy (dose and schedule).
Notably, feasibility and follow-up of surgery were also equivalent. Acute immune adverse events of short duration observed in 7.9% of patients.
The Injection site caused pain in 13.5% of patients. In addition, 6.7% of patients experienced grade 1 injection site hematoma / ecchymosis.
Regarding long-term toxicity, less serious adverse events were reported for NBTXR3 arm.
Regulatory strategy and CE mark
The positive results from this study support and further validate the European regulatory strategy of the previously submitted CE marking application in STS. The company will submit the new data as a supplement to the European Notified Body in a timely manner.
The Company will present the results at an upcoming international medical conference.
The clinical validation of NBTXR3’s physical mode of action in a very heterogeneous and hard-to-treat disease strengthens the universal profile of the product and confirms the development strategy in multiple indications.
Currently, the company is evaluating NBTXR3 in seven clinical trials with a focus on head and neck cancers and Immuno-Oncology programs.
David Raben MD, Professor of Radiation Oncology, University of Colorado Cancer Center, CO, USA, commented, “These results from a Phase III study are impressive in a notoriously difficult disease like Soft Tissue Sarcoma. These cancers are generally less sensitive to radiation and previous attempts to improve local control with chemo-radiation regimens were considered too toxic. This study substantiates the medical benefit of safely enhancing the effect of radiation therapy with novel physics-based approaches delivered locally within the cancer. In addition, this product may potentiate a pro-inflammatory environment suitable for immune enabling or DNA damage inhibitor drugs. These findings set the foundation for additional studies in areas such as head and neck cancer and perhaps in areas such as high-risk prostate, bladder or pancreas cancer.”